Structure of the lutropin/choriogonadotropin receptor.
In summary, the LH/CG receptor is a single polypeptide which contains a large hydrophilic domain that is situated extracellularly, attached to a region that spans the plasma membrane seven times, the carboxy-terminal region being intracellular. This topology was predicted by the amino acid sequence and has been confirmed by our immunofluorescence studies. The extracellular domain, which is related to a family of leucine-rich glycoproteins, is presumably involved in binding the large glycoprotein hormones hCG and LH. The carboxy-terminal half of the receptor, which is related to the family of rhodopsinlike receptors, is (by analogy with these receptors) presumably involved in the coupling of the receptor to the G protein. Our transfection studies confirm that this single polypeptide is capable of binding hormone and activating adenylyl cyclase. Therefore, not only is the structure of the LH/CG receptor unique compared to other cell surface receptors characterized to date, but also its structure suggests that the mechanism of the translation of hormone binding to G protein coupling in this receptor is different from other G protein-coupled receptors whose ligands are much smaller and intercalcate among the transmembrane helices. We predict that, due to the homology among the glycoprotein hormones, the structures of the FSH and TSH receptors share extensive amino acid and structural homology with the LH/CG receptor. Last, our newly acquired knowledge about the structure of the LH/CG receptor, and the development of a cDNA and antibodies for this receptor, should enable more detailed studies on the function and regulation of the LH/CG receptor, not previously possible.
Segaloff
D L
DL
Population Council, New York, New York 10021.
Sprengel
R
R
Nikolics
K
K
Ascoli
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006063:Chorionic Gonadotropin; D003432:Cross-Linking Reagents; D007163:Immunosorbent Techniques; D008969:Molecular Sequence Data; D011974:Receptors, LH / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology
D006063:Chorionic Gonadotropin; D003432:Cross-Linking Reagents; D011974:Receptors, LH